DESCRIPTION: The E1A and E1B oncogenes of adenovirus function during infection and transformation to control cell proliferation and apoptosis. E1A stimulates cell cycle progression by binding to Rb family members and to p300, which induces accumulation of p53 and leads to apoptosis. The E1B 19K protein, a member of the Bcl-2 family of apoptosis regulators, inhibits apoptosis and sustains virus infection. Induction of apoptosis by p53 is a complex process, involving many potential players, including Bax (an inducer of apoptosis) and the ICE family of cysteine proteases. The applicant will define the mechanism by which E1A induces the accumulation of p53, will identify the functional requirements within p53 for activation of cell death, and will determine the relationship between p53 function and activation of the ICE family proteases. The long term goal of the work is to study this important mechanism of tumor suppression.